Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2001-05-24
2002-12-31
Kumar, Shailendra (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S170000
Reexamination Certificate
active
06500980
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for preparing amino derivatives of C—H acid compounds of the general formula I:
where R is an unbranched or branched alkyl group having from 1 to 10 carbon atoms, in particular a methyl, ethyl or propyl radical, a cycloaliphatic radical having from 5 to 12 carbon atoms, an aryl radical, in particular a phenyl or a naphthyl radical, an alkylaryl radical having from 7 to 12 carbon atoms, such as the ethylphenyl radical, or an aralkyl radical having from 7 to 12 carbon atoms, such as the benzyl or the phenyl ethyl radical, and X
1
and X
2
are identical or different electron-withdrawing groups, by reacting C—H-acid compounds represented by formula II:
where X
1
and X
2
are as defined above,
with nitrous acid liberated from a nitrite by another acid, in the presence of from 1 to 10 mol of a carboxylic anhydride (based on the compound of the formula II), whereby practically complete conversion of the compound of the formula II is achieved, and the reaction product, the O-acyl derivative of the nitrosation product of II, is passed to a catalytic hydrogenation, optionally after removing the salts derived from the reaction.
2. Description of the Background
Amino derivatives represented by formula I are useful intermediates for compounds which can be used in the pharmaceutical and agricultural sectors. The corresponding N-acetamido malonic esters may be mentioned as examples.
There are a variety of processes known for the nitrosation of malonic acid derivatives, such as esters, amides, imidoesters and malononitrile.
For example, J.B. Paine et al. in J. Org. Chem. 50, 5598-5604 (1985), describe a process for preparing diethyl hydroxyiminomalonate, in which an aqueous solution of sodium nitrite is slowly added to a solution of diethyl malonate in glacial acetic acid, sodium hydroxide solution is added to the reaction mixture, which is a homogeneous solution, and the reaction product is removed from the aqueous phase comprising sodium acetate by extraction with diethyl ether. The process produces sodium acetate in the form of an aqueous solution in amounts which in molar terms are approximately 4 times the amount of diethyl malonate used.
In DE-A-23 52 706, ethyl cyanoacetate is first reacted with hydrogen chloride in absolute alcohol to give diethyl monoimidomalonate hydrochloride, and this is dissolved in acetic acid. An aqueous solution of sodium nitrite is then gradually added to the solution, and once the nitrosation reaction has ended, water is added to the reaction mixture. Again, the reaction product is removed from the aqueous phase which comprises the sodium acetate produced by extraction with a solvent.
EP-A-0 517 041 describes an example of the preparation of dimethyl hydroxyiminomalonate in which sodium nitrite and acetic acid are added to a mixture made from dimethyl malonate and water. The reaction mixture is extracted twice with dichloroethane, and the dimethyl hydroxyiminomalonate separated from the sodium acetate, which remains in the aqueous phase. Although the amounts of sodium nitrite used here are only 1.2 mol per mole of malonate, the reaction times of 21 hours make the reaction practically impossible to use for an industrial process. In addition, the process is not suitable for reacting malonic diesters of low water-solubility.
In all of the processes listed, the sodium acetate is produced as contaminated aqueous solutions which are difficult to dispose of. The processes are therefore unsuitable on environmental grounds for conversion to industrial scale.
DE 954 873 describes a process for preparing diethyl hydroxyiminomalonate, in which diethyl malonate is dissolved in a solvent which is not significantly water-miscible and which can be removed from the final product by distillation, for example toluene, and at least molar amounts of sodium nitrite, and also from 1 to 10% by weight of water, based on the malonic diester, are added to this solution, and glacial acetic acid is gradually added to the suspension at a temperature of from 30 to 70° C. until the nitrosation has been completed, and the reaction solution is separated off from undissolved sodium acetate, and diethyl hydroxyiminomalonate is crystallized from the solution. This process does not require solvent extraction and indeed about ⅔ of the sodium acetate is obtained as a solid. The process is said to give “smooth and rapid reactions and good yields”. However, at least the latter is not the case, because the crystalline product obtained with a melting point of from 86.5 to 88° C. is certainly not the diethyl hydroxyiminomalonate, but its complex with sodium acetate. The product is so impure that the hydrogenation to give the diethyl acetaminomalonate on platinum catalysts in acetic anhydride, which is a particularly advantageous solvent, is impossible.
European Patent Application EP-A-0 811 607 describes a process with which C—H-acid compounds of the general formula II, and in particular those of low water-solubility, can be reacted with only a slight excess of alkali metal nitrite with a short reaction time and high conversion, and with good yields, to give hydroxyimino or nitroso compounds with the high purity required for downstream reactions. The salts produced here as byproducts can substantially be obtained in solid, reusable form, and the production of highly contaminated wastewater can be substantially or completely avoided.
The process of EP-A-0 811 607 consists in nitrosating compounds of the general formula II in the presence of water and of an inert organic solvent, using nitrous acid liberated from a nitrite by another acid. Use is made here of inert organic solvents or, respectively, solvent mixtures, in each case giving reaction mixtures which are as far as possible homogeneous. The most part of the salts derived from the reaction precipitate after the reaction, and can be removed by filtration.
Suitable solvents given in EP-A-0 811 607 are aliphatic or alicyclic ethers, such as dibutyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane and dialkoxyalkanes. The examples of this European application mainly use 1,4-dioxane as solvent.
In the process described above there is >99% conversion of the compounds of the general formula II. Each of the nitrosation products is obtained in the form of the hydroxyimino compound or of the acetoxyimino compound, in yields of about 85% and with high purity.
EP A-0 811 607 expressly states that water is an indispensable constituent of the reaction mixture for the nitrosation reaction, since it permits and promotes the liberation of nitrous acid.
However, even if the process described in EPA-0 811 607 gives good yields of the corresponding nitrosation products, it nevertheless has numerous disadvantages.
The use of a solvent partially miscible with water, such as 1,4-dioxane, means that some or all of this solvent has to be removed from the reaction mixture after the reaction and prior to any further reaction, either by water-washing or by distillation. This is complicated and makes the preparation process considerably more expensive. In addition, the water-washing of the organic phase poses the problem that a not inconsiderable part of the abovementioned solvent passes into the washing water. The disposal of a resultant polluted wastewater is complicated and expensive. 1,4-Dioxane specifically, moreover, is a toxic solvent whose use is avoided where possible in industry.
EP-A-0 811 607 also describes the use of a second solvent, the addition of which after the nitrosation reaction brings about the substantial precipitation of the salts derived from the reaction. Methyl tert-butyl ether is highly suitable. To liberate the nitrous acid from the nitrite, the examples describe use acetic acid. After the nitrosation reaction and after the removal of the salts derived from the reaction, the reaction product is therefore present in a mixture of four different solvents—water, 1,4-dioxane, methyl tert-butyl ether and acetic acid. Prior to further reac
Bauer Frank
Kleemiss Wolfgang
Koehler Guenther
Degussa - AG
Kumar Shailendra
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